Intestinal transit-amplifying cells require METTL3 for growth factor signaling and cell survival

• DOI: 10.1172/jci.insight.171657
• Publication Date: 2023-10-26T16:01:41Z
• Authors: Charles H. Danan; Kaitlyn E. Naughton; Katharina E. Hayer; Sangeevan Vellappan; Emily A. McMillan; Yusen Zhou; Rina Matsuda; Shaneice K. Nettl...; Kay Katada; Louis R. Parham; Xianghui Ma; Afrah Chowdhury; Benjamin J. Wilkins; Premal Shah; Matthew D. Weitzman; Kathryn E. Hamilton
• Keywords: Homeostasis

Intestinal epithelial transit-amplifying cells are essential stem progenitors required for intestinal homeostasis, but their rapid proliferation renders them vulnerable to DNA damage from radiation and chemotherapy. Despite these cells' critical roles in homeostasis disease, few studies have described genes that cell function. We report RNA methyltransferase-like 3 (METTL3) is survival of the murine small intestine. Transit-amplifying death after METTL3 deletion was associated with crypt villus atrophy, loss absorptive enterocytes, uniform wasting METTL3-depleted mice. Sequencing polysome-bound methylated RNAs enteroids vivo demonstrated decreased translation hundreds transcripts deletion, particularly involved growth factor signal transduction such as Kras. Further investigation verified a relationship between Kras methylation protein levels vivo. Our study identifies an supporting tissue via direct maintenance survival. highlight crucial role modifications regulating signaling intestine important implications both homeostatic renewal regeneration.